The Clinic is the region's largest employer with roughly 42,000 workers.

Sheil said personnel represents 60 percent of the Clinic's budget.

She said early retirement would be offered to 3,000 eligible employees. Most vacant jobs are not being filled.

She attributed most of the budget reductions to looming changes accompanying the start of the Affordable Health Care Act.

Sheil said the Clinic had not made overall layoffs in the past 11 years.

She declined to give a specific figure on how many jobs could be lost.

Sheil said that depends on how much savings individual departments can make with other reductions.

She added that any layoffs would be across the board, including doctors.

The Clinic issued the following statement:

"To prepare for healthcare reform, Cleveland Clinic is transforming the way care is delivered to patients. Over the past several years, we have had an ongoing focus on driving efficiencies, lowering costs, reducing duplication in services and enhancing quality to make healthcare affordable to patients.

Although we have made progress, we need to further reduce costs to the organization by $330 million in 2014. We are carefully evaluating all aspects of our system to accomplish this. Some of the initiatives include offering early retirement to 3,000 eligible employees, reducing operational costs, stricter review of filling vacant positions, and lastly workforce reductions.

Through these changing times, we are focused on providing the highest quality of care to our patients in the most efficient and cost-effective manner."

Meanwhile, another major hospital in town, MetroHealth Medical Center, responded to the developments at the Cleveland Clinic.

"MetroHealth is well poised to meet the challenges and opportunities of the Affordable Care Act," said Dr. Akram Boutros, President and CEO of MetroHealth. "We have been gearing up and transforming the healthcare delivery process to improve patient care, outcomes and satisfaction, and reduce costs, which are essential elements for success under new models of reimbursement."

Metro did not comment on whether any future cuts are coming on its end. In 2011, the hospital system laid off 450 employees.